Many crucial biological processes take place in or adjacent to cellular membranes including receptor oligomerization, endocytosis, ligand-receptor binding, phosphorylation and de-phosphorylation of membrane proteins, folding and transport of newly synthesized proteins, viral invasion, immune reactions, and so on. Malfunctions in such processes can have profound effects on an organism's health and disease, e.g. Bunn et al, Semin. Oncol., 29 (5 Suppl 14): 38–44 (2002); Baker, Oncogene, 17: 3261–3270 (1998); and the like. For example, in some diseases, such as cancer, relationships have been identified between disease states and aberrancies in membrane molecules, e.g. Yarden, Oncology, 61: Suppl. 2: 1–13 (2001); Ouyang et al, Lancet, 353: 1591–1592 (1999); and the like. Because of such observations, there has been a great deal of interest and research in the cellular and molecular processes at membrane interfaces that relate to disease states, e.g. George et al, Nature Reviews Drug Discovery, 1: 808–820 (2002); Howard et al, Trends in Pharmaceutical Sciences, 22: 132–140 (2001); Seymour, Current Drug Targets, 2: 117–133 (2001). However, studying such processes has been challenging since they are often characterized by a highly complex interaction of many molecular components, e.g. Gutkind, Science STKE: 1–13 (2000); Weng et al, Science, 284: 92–96 (1999). It has been suggested that a full understanding of such complex phenomena requires a systems approach in which “global” measurements are made after systematic perturbations, e.g. Ideker et al, Annu. Rev. Genomics Hum. Genet., 2: 343–372 (2001). This approach has become feasible for some phenomena, such as gene expression in simple organisms where routine measurement of all, or large sets of, expressed genes is possible through the use of microarray technology, e.g. Nature Genetics Supplement, 32: 465–552 (December, 2002). However, for other phenomena, such as signal transduction pathways and other membrane-mediated processes, that involve the interaction of several to many tens of proteins, no comparable technology is available for making global or system-wide measurements.
In view of the above, the availability of a convenient and cost effective technique for measuring the presence or absence or quantities of multiple membrane-associated analytes, such as cell surface receptors, in a single assay reaction would advance the art in many fields where such measurements are becoming increasingly important, including life science research, medical research and diagnostics, drug discovery, animal and plant science, and the like.